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Investigation of in vitro wound healing properties of Salvia sclarea and Citrus aurantium essential oil combinations

Yıl 2024, Cilt: 28 Sayı: 5, 1820 - 1828, 28.06.2025

Ayşe Esra Karadağ , Betül Demirci , Zeynep Zişan Şakar Sevde Nur Biltekin

Öz

Salvia sclarea L. and Citrus aurantium L. are used ethnobotanically for wound treatment. The aim of this study was to evaluate phytochemical composition of Salvia sclarea L. and Citrus aurantium L. leaf essential oils and wound healing activities of their combinations. The phytochemical analysis was performed gas chromatography (GC) and mass spectroscopy (MS). Major components of S. sclarea leaf essential oil was confirmed both by GC-FID and GC/MS as 67% linalyl acetate, 20.2% linalool, 2.6%α-terpineole, respectively. The major components of C. aurantium leaf essential oil was also confirmed as 55% linalyl acetate, 23.4% linalool, 5.4%α-terpineole, respectively. Combinations of essential oils were loaded into Carbopol gel formulations. Wound healing activity of essential oil and combinations was investigated using in vitro scratch assay. As a result of the study, it was determined that the most effective wound healing concentration for Salvia sclarea essential oil was 50 µg/mL. The most effective concentration of Citrus aurantifolia essential oil was determined as 12.5 µg/mL. The aim of the study is to investigate the wound healing activities of the tested essential oils individually and in combination. The fact that no activity is observed in empty formulations is evidence that the activity of the loaded formulations does not come from empty formulations. It was observed that the loaded formulations showed better effects than the control Madecassol. Studies need to be confirmed by working under in vivo conditions.

Anahtar Kelimeler

Salvia sclarea Citrus aurantium wound healing essential oil

Kaynakça

  • [1] Doğanoğlu Ö, Gezer A, Yücedağ C. Göller Bölgesi-Yenişarbademli Yöresi'nin Önemli Bazı Tıbbi ve Aromatik Bitki Taksonları Üzerine Araştırmalar. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi. 2006; 10(1): 66-73.
  • [2] Yeşilada E, Honda G, Sezik E, Tabata M, Goto K, Ikeshiro Y. Traditional medicine in Turkey IV. Folk medicine in the Mediterranean subdivision. J Ethnopharm. 1993; 39(1): 31-38. https://doi.org/10.1016/0378-8741(93)90048-A
  • [3] Öğütçü H, Sökmen A, Sökmen M, Polissiou M, Serkedjieva J, Daferera D, Şahin F, Barış Ö, Güllüce M. Bioactivities of the various extracts and essential oils of Salvia limbata CA Mey. and Salvia sclarea L. Turk J Biol. 2008; 32(3): 181-192.
  • [4] Salimikia I, Aryanpour M, Bahramsoltani R, Abdollahi M, Abdolghaffari AH, Samadi N, Sabbaghziarani F, Gholami M, Monsef-Esfahani HR. Phytochemical and wound healing effects of methanolic extract of Salvia multicaulis Vahl. in rat. J. Med. Plants. 2016; 45 (2016): 38–46.
  • [5] Scrima M, Melito C, Merola F, Iorio A, Vito N, Giori AM, Ferravante A. Evaluation of Wound Healing Activity of Salvia haenkei Hydroalcoholic Aerial Part Extract on in vitro and in vivo Experimental Models. Clin Cosmet Investig Dermatol. 2020;13: 627. https://doi.org/10.2147/CCID.S224418
  • [6] Sienkiewicz M, Głowacka A, Poznańska-Kurowska K, Kaszuba A, Urbaniak A, Kowalczyk E. The effect of clary sage oil on staphylococci responsible for wound infections. Postępy Dermatol Alergol. 2015;32(1): 21. https://doi.org/10.5114/pdia.2014.40957
  • [7] Suntar I, Khan H, Patel S, Celano R, Rastrelli L. An overview on Citrus aurantium L.: Its functions as food ingredient and therapeutic agent. Oxid Med Cell Longev. 2018;2018(1): 7864269. https://doi.org/10.1155/2018/7864269
  • [8] Polo CM, Moraes TM, Pellizzon CH, Marques MO, Rocha LRM, Hiruma-Lima CA. Gastric Ulcers in Middle‐Aged Rats: The Healing Effect of Essential Oil from Citrus aurantium L. (Rutaceae). Evid Based Complementary Altern Med. 2012;2012(1): 509451. https://doi.org/10.1155/2012/509451
  • [9] Cherukuri S, Paramanayagam A, Prabakaran R, Mayakannan M, Vuppalapati L. Evaluation of cutaneous wound healing activity of Citrus aurantium Fruit Peel extract-based ointment in albino rats. Res J Pharm Technol. 2023;16(1): 250-254. https://doi.org/10.52711/0974-360X.2023.00046
  • [10] Dorai AA. Wound care with traditional, complementary and alternative medicine. Indian J Plast Surg. 2012; 45(2): 418-424. https://doi.org/10.4103/0970-0358.101331
  • [11] Reza FM. Medicinal plants in wound healing, wound healing current perspectives. Intech Open. 2019;2019:37- 47. https://doi.org/10.5772/intechopen.80215
  • [12] Shah A, Amini-Nik S. The role of phytochemicals in the inflammatory phase of of wound healing. Int J Mol Sci. 2017;18(5): 1068. https://doi.org/10.3390/ijms18051068
  • [13] Salas-Oropeza J, Rodriguez-Monroy MA, Jimenez-Estrada M, Perez-Torres A, Castell-Rodriguez AE, Becerril-Millan R, Canales-Martinez MM. Essential Oil of Bursera morelensis Promotes Cell Migration on Fibroblasts: In Vitro Assays. Molecules, 2023 ;28(17) : 6258. https://doi.org/10.3390/molecules28176258
  • [14] Yuce E, Yildirim N, Yildirim NC, Paksoy MY, Bagci E. Essential oil composition, antioxidant and antifungal activities of Salvia sclarea L. from Munzur Valley in Tunceli. Cell Mol Biol. 2014; 60(2): 1-5. https://doi.org/10.14715/cmb/2014.60.2.1
  • [15] Al-Aamri MS, Al-Abousi NM, Al-Jabri SS, Alam T, Khan SA. Chemical composition and in-vitro antioxidant and antimicrobial activity of the essential oil of Citrus aurantifolia L. leaves grown in Eastern Oman. J Taibah Univ Sci. 2018:13(2); 108-112. https://doi.org/10.1016/j.jtumed.2017.12.002
  • [16] Krismaya I, Pramudya R, Sati P, Kamadjaja DB. Effects of lime (Citrus aurantifolia christm. swingle) peel extract on fibroblast proliferation and angiogenesis in rat’s tooth extraction sockets. Angiogenesis, 2019 ;19(2) : 1-3. https://doi.org/10.35124/bca.2019.19.S2.4917
  • [17] Tsai HC, Li YC, Young TH, Chen MH. Citrus polyphenol for oral wound healing in oral ulcers and periodontal diseases. J Formos Med Assoc. 2016;115(2): 100-107. https://doi.org/10.1016/j.jfma.2015.01.003
  • [18] Moraes TM, Rozza AL, Kushima H, Pellizzon CH, Rocha LRM, Hiruma-Lima CA. Healing actions of essential oils from Citrus aurantium and d-limonene in the gastric mucosa: the roles of VEGF, PCNA, and COX-2 in cell proliferation. J Med Food. 2013; 16(12): 1162-1167. https://doi.org/10.1089/jmf.2012.025
  • [19] Syafri S, Husni E, Wafiqah N, Ramadhan F, Ramadani S, Hamidi D. Evaluation of Antimicrobial and Proliferation of Fibroblast Cells Activities of Citrus Essential Oils. Open Access Maced J Med Sci. 2020;10(A): 1051-1057. https://doi.org/10.3889/oamjms.2022.8596
  • [20] Majnooni MB, Mansouri K, Gholivand MB, Mostafaie A, Mohammadi-Motlagh HR, Afnanzade NS, Piriyaei M. Chemical composition, cytotoxicity and antioxidant activities of the essential oil from the leaves of Citrus aurantium L. Afr J Biotechnol. 2012;11(2): 498-503. https://doi.org/10.5897/AJB11.1449
  • [21] Zain MH, Hasan Al-Ismaeel WN, Al-Jaber GT. Cytotoxic and Antioxidant Activities of Clary Sage (Salvia sclarea L.) Essential Oil Against AMJ-13 Cancer Cell Line. Trop J Nat Prod Res. 2022;6(5): 732-735. https://doi.org/10.26538/tjnpr/v6i5.12
  • [22] Demirci F, Karadağ AE, Biltekin SN, Demirci B. In vitro ACE2 and 5-LOX enzyme inhibition by menthol and three different mint essential oils. Nat Prod Comm. 2021;16(11):1934578X211055014. https://doi.org/10.1177/1934578X211055014
  • [23] Okur ME, Karadağ AE, Üstündağ Okur N, Özhan Y, Sipahi H, Ayla Ş, Demirci F. In vivo wound healing and in vitro anti-inflammatory activity evaluation of Phlomis russeliana extract gel formulations. Molecules. 2020;25(11): 2695. https://dx.doi.org/10.3390/molecules25112695
  • [24] Karadağ AE, Biltekin SN, Demirci B, Demirci F, Ghani U. Comparative in vitro and in silico enzyme inhibitory screening of rosa x damascena and pelargonium graveolens essential oils and geraniol. Plants, 2023;12(18): 3296. https://doi.org/10.3390/plants12183296
  • [25] Karadağ AE, Çaşkurlu A, Okur ME, Guzelmeric E, Okur NÜ, Tosun F, Yeşilada E, Demirci F. Hemostatic activity of cistus creticus extract in Wistar albino rats. Rev Bras Farmacogn. 2020;30: 844-847. https://doi.org/10.1007/s43450-020-00120-7

Yıl 2024, Cilt: 28 Sayı: 5, 1820 - 1828, 28.06.2025

Ayşe Esra Karadağ , Betül Demirci , Zeynep Zişan Şakar Sevde Nur Biltekin

Öz

Kaynakça

  • [1] Doğanoğlu Ö, Gezer A, Yücedağ C. Göller Bölgesi-Yenişarbademli Yöresi'nin Önemli Bazı Tıbbi ve Aromatik Bitki Taksonları Üzerine Araştırmalar. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi. 2006; 10(1): 66-73.
  • [2] Yeşilada E, Honda G, Sezik E, Tabata M, Goto K, Ikeshiro Y. Traditional medicine in Turkey IV. Folk medicine in the Mediterranean subdivision. J Ethnopharm. 1993; 39(1): 31-38. https://doi.org/10.1016/0378-8741(93)90048-A
  • [3] Öğütçü H, Sökmen A, Sökmen M, Polissiou M, Serkedjieva J, Daferera D, Şahin F, Barış Ö, Güllüce M. Bioactivities of the various extracts and essential oils of Salvia limbata CA Mey. and Salvia sclarea L. Turk J Biol. 2008; 32(3): 181-192.
  • [4] Salimikia I, Aryanpour M, Bahramsoltani R, Abdollahi M, Abdolghaffari AH, Samadi N, Sabbaghziarani F, Gholami M, Monsef-Esfahani HR. Phytochemical and wound healing effects of methanolic extract of Salvia multicaulis Vahl. in rat. J. Med. Plants. 2016; 45 (2016): 38–46.
  • [5] Scrima M, Melito C, Merola F, Iorio A, Vito N, Giori AM, Ferravante A. Evaluation of Wound Healing Activity of Salvia haenkei Hydroalcoholic Aerial Part Extract on in vitro and in vivo Experimental Models. Clin Cosmet Investig Dermatol. 2020;13: 627. https://doi.org/10.2147/CCID.S224418
  • [6] Sienkiewicz M, Głowacka A, Poznańska-Kurowska K, Kaszuba A, Urbaniak A, Kowalczyk E. The effect of clary sage oil on staphylococci responsible for wound infections. Postępy Dermatol Alergol. 2015;32(1): 21. https://doi.org/10.5114/pdia.2014.40957
  • [7] Suntar I, Khan H, Patel S, Celano R, Rastrelli L. An overview on Citrus aurantium L.: Its functions as food ingredient and therapeutic agent. Oxid Med Cell Longev. 2018;2018(1): 7864269. https://doi.org/10.1155/2018/7864269
  • [8] Polo CM, Moraes TM, Pellizzon CH, Marques MO, Rocha LRM, Hiruma-Lima CA. Gastric Ulcers in Middle‐Aged Rats: The Healing Effect of Essential Oil from Citrus aurantium L. (Rutaceae). Evid Based Complementary Altern Med. 2012;2012(1): 509451. https://doi.org/10.1155/2012/509451
  • [9] Cherukuri S, Paramanayagam A, Prabakaran R, Mayakannan M, Vuppalapati L. Evaluation of cutaneous wound healing activity of Citrus aurantium Fruit Peel extract-based ointment in albino rats. Res J Pharm Technol. 2023;16(1): 250-254. https://doi.org/10.52711/0974-360X.2023.00046
  • [10] Dorai AA. Wound care with traditional, complementary and alternative medicine. Indian J Plast Surg. 2012; 45(2): 418-424. https://doi.org/10.4103/0970-0358.101331
  • [11] Reza FM. Medicinal plants in wound healing, wound healing current perspectives. Intech Open. 2019;2019:37- 47. https://doi.org/10.5772/intechopen.80215
  • [12] Shah A, Amini-Nik S. The role of phytochemicals in the inflammatory phase of of wound healing. Int J Mol Sci. 2017;18(5): 1068. https://doi.org/10.3390/ijms18051068
  • [13] Salas-Oropeza J, Rodriguez-Monroy MA, Jimenez-Estrada M, Perez-Torres A, Castell-Rodriguez AE, Becerril-Millan R, Canales-Martinez MM. Essential Oil of Bursera morelensis Promotes Cell Migration on Fibroblasts: In Vitro Assays. Molecules, 2023 ;28(17) : 6258. https://doi.org/10.3390/molecules28176258
  • [14] Yuce E, Yildirim N, Yildirim NC, Paksoy MY, Bagci E. Essential oil composition, antioxidant and antifungal activities of Salvia sclarea L. from Munzur Valley in Tunceli. Cell Mol Biol. 2014; 60(2): 1-5. https://doi.org/10.14715/cmb/2014.60.2.1
  • [15] Al-Aamri MS, Al-Abousi NM, Al-Jabri SS, Alam T, Khan SA. Chemical composition and in-vitro antioxidant and antimicrobial activity of the essential oil of Citrus aurantifolia L. leaves grown in Eastern Oman. J Taibah Univ Sci. 2018:13(2); 108-112. https://doi.org/10.1016/j.jtumed.2017.12.002
  • [16] Krismaya I, Pramudya R, Sati P, Kamadjaja DB. Effects of lime (Citrus aurantifolia christm. swingle) peel extract on fibroblast proliferation and angiogenesis in rat’s tooth extraction sockets. Angiogenesis, 2019 ;19(2) : 1-3. https://doi.org/10.35124/bca.2019.19.S2.4917
  • [17] Tsai HC, Li YC, Young TH, Chen MH. Citrus polyphenol for oral wound healing in oral ulcers and periodontal diseases. J Formos Med Assoc. 2016;115(2): 100-107. https://doi.org/10.1016/j.jfma.2015.01.003
  • [18] Moraes TM, Rozza AL, Kushima H, Pellizzon CH, Rocha LRM, Hiruma-Lima CA. Healing actions of essential oils from Citrus aurantium and d-limonene in the gastric mucosa: the roles of VEGF, PCNA, and COX-2 in cell proliferation. J Med Food. 2013; 16(12): 1162-1167. https://doi.org/10.1089/jmf.2012.025
  • [19] Syafri S, Husni E, Wafiqah N, Ramadhan F, Ramadani S, Hamidi D. Evaluation of Antimicrobial and Proliferation of Fibroblast Cells Activities of Citrus Essential Oils. Open Access Maced J Med Sci. 2020;10(A): 1051-1057. https://doi.org/10.3889/oamjms.2022.8596
  • [20] Majnooni MB, Mansouri K, Gholivand MB, Mostafaie A, Mohammadi-Motlagh HR, Afnanzade NS, Piriyaei M. Chemical composition, cytotoxicity and antioxidant activities of the essential oil from the leaves of Citrus aurantium L. Afr J Biotechnol. 2012;11(2): 498-503. https://doi.org/10.5897/AJB11.1449
  • [21] Zain MH, Hasan Al-Ismaeel WN, Al-Jaber GT. Cytotoxic and Antioxidant Activities of Clary Sage (Salvia sclarea L.) Essential Oil Against AMJ-13 Cancer Cell Line. Trop J Nat Prod Res. 2022;6(5): 732-735. https://doi.org/10.26538/tjnpr/v6i5.12
  • [22] Demirci F, Karadağ AE, Biltekin SN, Demirci B. In vitro ACE2 and 5-LOX enzyme inhibition by menthol and three different mint essential oils. Nat Prod Comm. 2021;16(11):1934578X211055014. https://doi.org/10.1177/1934578X211055014
  • [23] Okur ME, Karadağ AE, Üstündağ Okur N, Özhan Y, Sipahi H, Ayla Ş, Demirci F. In vivo wound healing and in vitro anti-inflammatory activity evaluation of Phlomis russeliana extract gel formulations. Molecules. 2020;25(11): 2695. https://dx.doi.org/10.3390/molecules25112695
  • [24] Karadağ AE, Biltekin SN, Demirci B, Demirci F, Ghani U. Comparative in vitro and in silico enzyme inhibitory screening of rosa x damascena and pelargonium graveolens essential oils and geraniol. Plants, 2023;12(18): 3296. https://doi.org/10.3390/plants12183296
  • [25] Karadağ AE, Çaşkurlu A, Okur ME, Guzelmeric E, Okur NÜ, Tosun F, Yeşilada E, Demirci F. Hemostatic activity of cistus creticus extract in Wistar albino rats. Rev Bras Farmacogn. 2020;30: 844-847. https://doi.org/10.1007/s43450-020-00120-7
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Ayşe Esra Karadağ 0000-0002-3412-0807

Betül Demirci

Zeynep Zişan Şakar 0009-0000-8551-397X

Sevde Nur Biltekin 0000-0003-1896-2729

Yayımlanma Tarihi 28 Haziran 2025
Gönderilme Tarihi 25 Temmuz 2024
Kabul Tarihi 23 Ağustos 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 28 Sayı: 5

Kaynak Göster

APA Karadağ, A. E., Demirci, B., Şakar, Z. Z., Biltekin, S. N. (2025). Investigation of in vitro wound healing properties of Salvia sclarea and Citrus aurantium essential oil combinations. Journal of Research in Pharmacy, 28(5), 1820-1828.
AMA Karadağ AE, Demirci B, Şakar ZZ, Biltekin SN. Investigation of in vitro wound healing properties of Salvia sclarea and Citrus aurantium essential oil combinations. J. Res. Pharm. Temmuz 2025;28(5):1820-1828.
Chicago Karadağ, Ayşe Esra, Betül Demirci, Zeynep Zişan Şakar, ve Sevde Nur Biltekin. “Investigation of in Vitro Wound Healing Properties of Salvia Sclarea and Citrus Aurantium Essential Oil Combinations”. Journal of Research in Pharmacy 28, sy. 5 (Temmuz 2025): 1820-28.
EndNote Karadağ AE, Demirci B, Şakar ZZ, Biltekin SN (01 Temmuz 2025) Investigation of in vitro wound healing properties of Salvia sclarea and Citrus aurantium essential oil combinations. Journal of Research in Pharmacy 28 5 1820–1828.
IEEE A. E. Karadağ, B. Demirci, Z. Z. Şakar, ve S. N. Biltekin, “Investigation of in vitro wound healing properties of Salvia sclarea and Citrus aurantium essential oil combinations”, J. Res. Pharm., c. 28, sy. 5, ss. 1820–1828, 2025.
ISNAD Karadağ, Ayşe Esra vd. “Investigation of in Vitro Wound Healing Properties of Salvia Sclarea and Citrus Aurantium Essential Oil Combinations”. Journal of Research in Pharmacy 28/5 (Temmuz 2025), 1820-1828.
JAMA Karadağ AE, Demirci B, Şakar ZZ, Biltekin SN. Investigation of in vitro wound healing properties of Salvia sclarea and Citrus aurantium essential oil combinations. J. Res. Pharm. 2025;28:1820–1828.
MLA Karadağ, Ayşe Esra vd. “Investigation of in Vitro Wound Healing Properties of Salvia Sclarea and Citrus Aurantium Essential Oil Combinations”. Journal of Research in Pharmacy, c. 28, sy. 5, 2025, ss. 1820-8.
Vancouver Karadağ AE, Demirci B, Şakar ZZ, Biltekin SN. Investigation of in vitro wound healing properties of Salvia sclarea and Citrus aurantium essential oil combinations. J. Res. Pharm. 2025;28(5):1820-8.